Glucocorticoid-Induced Apoptosis

Abstract

Publisher Summary In present days, glucocorticoids are a mainstay of the therapeutic armamentarium for lymphomas and other lymphocytic malignancies. When treated with glucocorticoids, malignant lymphocytes isolated from blood or bone marrow of patients undergo programmed cell death, or apoptosis. However, the fact that malignant lymphocytes have a propensity to become resistant to glucocorticoids is significantly limiting its therapeutic efficacy. A detailed understanding of the mechanism of glucocorticoid-induced apoptosis is likely to translate into new therapeutic possibilities for lymphoid malignancies, including methods for circumventing or overcoming glucocorticoid resistance. This chapter addresses a working model of glucocorticoid-induced apoptosis. This model is founded on existing knowledge regarding the mechanism of glucocorticoid-induced cell death in lymphocytes and thymocytes, together with emerging evidence from other experimental systems. Based on the genetic pathway for programmed cell death recently unraveled in the primitive nematode Caeizorhahditis elgans, cell death in glucocorticoid-treated lymphocytes is viewed as a genetically regulated, stepwise process beginning with the decision of the healthy lymphocyte to die, the execution of the death program, engulfment by other cells, and degradation. The model reveals existing gaps in understanding, thereby identifying both long-standing unresolved questions and new questions of pressing importance.